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Humanized Anti-Carcinoembryonic Antigen Antibodies Brightly Target and Label Gastric Cancer in Orthotopic Mouse
Kristin E Cox1, Michael A Turner1, Siamak Amirfakhri1
1Department of Surgery, University of California San Diego, La Jolla, California; Department of Surgery, VA San Diego Healthcare System, La Jolla, California.
Introduction:
Gastric cancer poses a major therapeutic challenge. Improved visualization of tumor margins at the time of gastrectomy with fluorescent tumor-specific antibodies could improve outcomes. The present report demonstrates the potential of targeting gastric cancer with a humanized anti-carcinoembryonic antigen (CEA) antibody in orthotopic mouse models.
Methods:
MKN45 cells were injected subcutaneously into nude mice to establish xenograft models. Tumor fragments collected from subcutaneous models were then implanted into the greater curvature of the stomach to establish orthotopic models. For tumor labeling, a humanized anti-CEA antibody (M5A) and IgG as a control, were conjugated with the near-infrared dye IRDye800CW. Time (24-72 h) and dose (50-100 μg) response curves were performed in subcutaneous models. Orthotopic models received 50 μg of M5A-IR800 or 50 μg IgG-IR800 as a control and were imaged after 72 h. Fluorescence imaging was performed on the mice using the LI-COR Pearl Imaging System.
Results:
In subcutaneous models, tumor to background ratios (TBRs) reached 8.85 at 72 h. Median TBRs of orthotopic model primary tumors were 6.25 (interquartile range [IQR] 6.03-7.12) for M5A-IR800 compared to 0.42 (IQR 0.38-0.54) for control. Abdominal wall metastasis median TBRs were 13.52 (IQR 12.79-13.76) for M5A-IR800 and 3.19 (IQR 2.65-3.73) for the control. Immunohistochemistry confirmed CEA expression within tumors.
Conclusions:
Humanized anti-CEA antibodies conjugated to near-infrared dyes provide specific labeling of gastric cancers in mouse models. Orthotopic models demonstrated bright and specific labeling with TBRs greater than ten times that of control. This tumor-specific fluorescent antibody is a promising potential clinical tool for improving visualization of gastric cancer margins at time of surgical resection.
Insights
A novel humanized anti-carcinoembryonic antigen (CEA) antibody, conjugated to a near-infrared dye, effectively visualizes gastric cancer in mouse models. This fluorescent antibody shows promise for improving surgical margin detection during gastrectomy.
Area of Science:
- Oncology
- Medical Imaging
- Immunotherapy
Background:
- Gastric cancer presents significant therapeutic challenges.
- Accurate visualization of tumor margins during surgery is crucial for improved patient outcomes.
- Fluorescent tumor-specific antibodies offer a potential method for enhanced intraoperative margin detection.
Purpose of the Study:
- To evaluate the efficacy of a humanized anti-carcinoembryonic antigen (CEA) antibody conjugated to a near-infrared dye for specific labeling of gastric cancer.
- To assess the antibody's performance in both subcutaneous and orthotopic mouse models.
- To determine the potential of this targeted fluorescent approach as a clinical tool for surgical guidance.
Main Methods:
- Gastric cancer xenograft models were established using MKN45 cells in nude mice.
- A humanized anti-CEA antibody (M5A) was conjugated with IRDye800CW near-infrared dye.
- Tumor labeling and fluorescence imaging were performed in subcutaneous and orthotopic models, with dose and time-response studies.
- Tumor-to-background ratios (TBRs) were quantified, and CEA expression was confirmed via immunohistochemistry.
Main Results:
- In subcutaneous models, tumor-to-background ratios (TBRs) reached 8.85 at 72 hours.
- Orthotopic models showed significantly higher median TBRs for primary tumors (6.25) and abdominal wall metastases (13.52) with the anti-CEA antibody compared to controls (0.42 and 3.19, respectively).
- Immunohistochemistry confirmed specific CEA expression within the tumors, validating the antibody's targeting.
Conclusions:
- Humanized anti-CEA antibodies conjugated to near-infrared dyes enable specific and effective fluorescent labeling of gastric cancer in preclinical models.
- The developed fluorescent antibody demonstrated bright and specific tumor labeling in orthotopic models, with TBRs over ten times higher than controls.
- This targeted fluorescent antibody represents a promising tool for enhancing the visualization of gastric cancer margins during surgical resection.
